Pembrolizumab for Advanced Prostate Adenocarcinoma: Findings of the KEYNOTE-028 Study

BACKGROUND: Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented. 

MATERIALS AND METHODS: Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥1% of tumor or stromal cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by investigator review.

RESULTS: Median patient age in this cohort (n = 23) was 65 years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% [95% confidence interval (CI) 5.0%-38.8%]; 8 of 23 (34.8%) patients had stable disease. The median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred.

CONCLUSION: Pembrolizumab resulted in a durable objective response in a subset of patients with heavily pretreated, advanced PD-L1-positive prostate cancer, and its side effect profile was favorable.
Clinical identifier: NCT02054806.

Annals of Oncology. 2018 July 09 [Epub ahead of print]

A.R. Hansen,1 C. Massard,2 P.A. Ott,3 N.B. Haas,4 J.S. Lopez,5 S. Ejadi,6 J.M. Wallmark,7 B. Keam,8 J-P. Delord,9 R. Aggarwal,10 M. Gould,11 P. Yang,11 S.M. Keefe,11 S.A. Piha-Paul12
1. Division of Medical Oncology, UHN Princess Margaret Cancer Centre, Toronto, Ontario, Canada
2. Department of Medical Oncology, Gustave Roussy, Villejuif, France
3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
4. Division of Hematology Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
5. The Royal Marsden and the Institute of Cancer Research, London, United Kingdom
6. Department of Medical Oncology, Virginia G. Piper Cancer Center at HonorHealth, Scottsdale, Arizona
7. Department of Medical Oncology, Associates in Oncology & Hematology, Rockville, Maryland
8. Department of HematoOncology, Seoul National University Hospital, Seoul, Republic of Korea
9. Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France
10. Department of Medicine, Division of Hematology/Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
11. Department of Oncology, Merck & Co., Inc, Kenilworth, New Jersey
12. Department of Investigational Clinical Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas